State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, China.
Molecules. 2023 Jun 22;28(13):4914. doi: 10.3390/molecules28134914.
Connexin 43 (Cx43) is most widely distributed in mammals, especially in the cardiovascular and nervous systems. Its phosphorylation state has been found to be regulated by the action of more than ten kinases and phosphatases, including mitogen-activated protein kinase/extracellular signaling and regulating kinase signaling. In addition, the phosphorylation status of different phosphorylation sites affects its own synthesis and assembly and the function of the gap junctions (GJs) to varying degrees. The phosphorylation of Cx43 can affect the permeability, electrical conductivity, and gating properties of GJs, thereby having various effects on intercellular communication and affecting physiological or pathological processes in vitro and in vivo. Therefore, clarifying the relationship between Cx43 phosphorylation and specific disease processes will help us better understand the disease. Based on the above clinical and preclinical findings, we present in this review the functional significance of Cx43 phosphorylation in multiple diseases and discuss the potential of Cx43 as a drug target in Cx43-related disease pathophysiology, with an emphasis on the importance of connexin 43 as an emerging therapeutic target in cardiac and neuroprotection.
间隙连接蛋白 43（Cx43）在哺乳动物中分布最广泛，尤其是在心血管和神经系统中。已经发现其磷酸化状态受到十多种激酶和磷酸酶的调节，包括丝裂原激活蛋白激酶/细胞外信号调节激酶信号通路。此外，不同磷酸化位点的磷酸化状态会在不同程度上影响其自身的合成和组装以及间隙连接（GJ）的功能。Cx43 的磷酸化可以影响 GJ 的通透性、电导率和门控特性，从而对细胞间通讯产生各种影响，并影响体外和体内的生理或病理过程。因此，阐明 Cx43 磷酸化与特定疾病过程之间的关系将有助于我们更好地了解疾病。基于上述临床前和临床发现，我们在这篇综述中介绍了 Cx43 磷酸化在多种疾病中的功能意义，并讨论了 Cx43 作为 Cx43 相关疾病病理生理学中药物靶点的潜力，重点强调了 connexin 43 作为心脏和神经保护中新兴治疗靶点的重要性。
